Investigating the effects of CD137 agonist on dendritic cell heterogeneity and population of mature regulatory dendritic cells

Abstract

CD137 is one of the receptors present on the surface of immune cells which are activated in presence of a ligand and is responsible for causing mediation of immune response during inflammatory reactions. In the case of dendritic cells, they can lead to a change in the heterogeneity of their population by causing maturation and migration of these cells, leading to change in the population depending on the function of each individual groups. It is originally speculated that injection of the CD137 ligand, which in this case is the agonistic antibody, will cause an increase in the cDC2 population as well as the mregDC2 cells as the antibody will ultimately cause immunosuppression. In order to confirm this hypothesis we injected the agonistic antibody into GVHD-induced mice which have chronically elevated inflammatory response and conducted scRNA-seq to analyze the change in the cell population of each type of immune cell. Although our research was not able to confirm the increase in the cDC2 and mregDC2 population, we were able to identify that CD137 antibody does indeed cause certain change in the dendritic cell population dynamics in such a way that the cells originally present in the control group mature and migrate into other forms of immune cells. We also consequently conducted ATAC-seq on both cDC2 and mregDC2 samples to discover possible mechanisms behind such changes yet wasn’t successful. Our paper seeks to provide a starting point and presents possibilities which can serve as a foundation for any further research that can be done on this topic.